D-2-Hydroxyglutarate dehydrogenase plays a dual role in L-serine biosynthesis and D-malate utilization in the bacterium Pseudomonas stutzeri

Pseudomonas is a very large bacterial genus in which several species can use d-malate for growth. However, the enzymes that can metabolize d-malate, such as d-malate dehydrogenase, appear to be absent in most Pseudomonas species. d-3-Phosphoglycerate dehydrogenase (SerA) can catalyze the production of d-2-hydroxyglutarate (d-2-HG) from 2-ketoglutarate to support d-3-phosphoglycerate dehydrogenation, which is the initial reaction in bacterial l-serine biosynthesis. In this study, we show that SerA of the Pseudomonas stutzeri strain A1501 reduces oxaloacetate to d-malate and that d-2-HG dehydrogenase (D2HGDH) from P. stutzeri displays d-malate–oxidizing activity. Of note, D2HGDH participates in converting a trace amount of d-malate to oxaloacetate during bacterial l-serine biosynthesis. Moreover, D2HGDH is crucial for the utilization of d-malate as the sole carbon source for growth of P. stutzeri A1501. We also found that the D2HGDH expression is induced by the exogenously added d-2-HG or d-malate and that a flavoprotein functions as a soluble electron carrier between D2HGDH and electron transport chains to support d-malate utilization by P. stutzeri. These results support the idea that D2HGDH evolves as an enzyme for both d-malate and d-2-HG dehydrogenation in P. stutzeri. In summary, D2HGDH from P. stutzeri A1501 participates in both a core metabolic pathway for l-serine biosynthesis and utilization of extracellular d-malate.